Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431

Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals...

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Autores principales:	Mariya Vildanova, Polina Vishnyakova, Aleena Saidova, Victoria Konduktorova, Galina Onishchenko, Elena Smirnova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autophagy differentiation epidermoid carcinoma ER stress gibberellic acid human keratinocytes Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/854cbb91ad864663b61f2c69aacefe88
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spelling	oai:doaj.org-article:854cbb91ad864663b61f2c69aacefe882021-11-25T18:40:52ZGibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A43110.3390/pharmaceutics131118131999-4923https://doaj.org/article/854cbb91ad864663b61f2c69aacefe882021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1813https://doaj.org/toc/1999-4923Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals and humans, influencing specific cellular functions and metabolic pathways. However, the effect of GA on animal and human cells remains controversial. We investigated the effect of GA on cultured human cell lines of epidermoid origin—immortalized non-tumorigenic keratinocytes HaCaT and carcinoma A431 cells. We found that at a non-toxic dose, GA upregulated the expression of genes associated with the ER stress response—<i>CHOP</i>, <i>sXBP1</i>, <i>GRP87</i> in both cell lines, and <i>ATF4</i> predominantly in A431 cells. We also showed that GA was more effective in upregulating the production of ER stress marker GRP78, autophagy marker LC3B-II, and differentiation markers involucrin and filaggrin in A431 cells than in HaCaT. We conclude that GA induces mild ER stress in both cell lines, followed by the activation of differentiation via upregulation of autophagy. However, in comparison with immortalized keratinocytes HaCaT, GA is more effective in inducing differentiation of carcinoma A431 cells, probably due to the inherently lower differentiation status of A431 cells. The activation of differentiation in poorly differentiated and highly malignant A431 cells by GA may lower the level of malignancy of these cells and decrease their tumorigenic potential.Mariya VildanovaPolina VishnyakovaAleena SaidovaVictoria KonduktorovaGalina OnishchenkoElena SmirnovaMDPI AGarticleautophagydifferentiationepidermoid carcinomaER stressgibberellic acidhuman keratinocytesPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1813, p 1813 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy differentiation epidermoid carcinoma ER stress gibberellic acid human keratinocytes Pharmacy and materia medica RS1-441
spellingShingle	autophagy differentiation epidermoid carcinoma ER stress gibberellic acid human keratinocytes Pharmacy and materia medica RS1-441 Mariya Vildanova Polina Vishnyakova Aleena Saidova Victoria Konduktorova Galina Onishchenko Elena Smirnova Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
description	Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals and humans, influencing specific cellular functions and metabolic pathways. However, the effect of GA on animal and human cells remains controversial. We investigated the effect of GA on cultured human cell lines of epidermoid origin—immortalized non-tumorigenic keratinocytes HaCaT and carcinoma A431 cells. We found that at a non-toxic dose, GA upregulated the expression of genes associated with the ER stress response—<i>CHOP</i>, <i>sXBP1</i>, <i>GRP87</i> in both cell lines, and <i>ATF4</i> predominantly in A431 cells. We also showed that GA was more effective in upregulating the production of ER stress marker GRP78, autophagy marker LC3B-II, and differentiation markers involucrin and filaggrin in A431 cells than in HaCaT. We conclude that GA induces mild ER stress in both cell lines, followed by the activation of differentiation via upregulation of autophagy. However, in comparison with immortalized keratinocytes HaCaT, GA is more effective in inducing differentiation of carcinoma A431 cells, probably due to the inherently lower differentiation status of A431 cells. The activation of differentiation in poorly differentiated and highly malignant A431 cells by GA may lower the level of malignancy of these cells and decrease their tumorigenic potential.
format	article
author	Mariya Vildanova Polina Vishnyakova Aleena Saidova Victoria Konduktorova Galina Onishchenko Elena Smirnova
author_facet	Mariya Vildanova Polina Vishnyakova Aleena Saidova Victoria Konduktorova Galina Onishchenko Elena Smirnova
author_sort	Mariya Vildanova
title	Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
title_short	Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
title_full	Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
title_fullStr	Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
title_full_unstemmed	Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431
title_sort	gibberellic acid initiates er stress and activation of differentiation in cultured human immortalized keratinocytes hacat and epidermoid carcinoma cells a431
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/854cbb91ad864663b61f2c69aacefe88
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Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431

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